Πέμπτη 15 Μαρτίου 2018

Inspiratory muscle training improves physical performance and cardiac autonomic modulation in older women

Abstract

Purpose

Aging impairs the autonomic balance reducing the vagal and increasing the sympathetic components of heart rate variability (HRV) and this could be associated with a decline in physical capacity. Inspiratory muscle training (IMT) is a possible tool to attenuate this physical capacity decline in older women. The aim of this study was to investigate the influence of IMT in the older women on physical capacity and autonomic cardiac modulation at rest and post exercise.

Methods

20 female participants 60–72 years old were randomly allocated in two groups. One group underwent IMT set at 50% of maximum inspiratory pressure (MIP), every day for 4 weeks (IMT-group). The placebo group performed the same training procedure but with a minimal resistance (5% MIP; PLA-group). Every week, the IMT load was readjusted and the HRV evaluated at rest. The six-minute walk test (6MWT) was performed once pre and post IMT-intervention. The IMT-group and PLA-group performed the same test and intervention procedures.

Results

After a 5 weeks intervention, the MIP had significantly improved in the IMT-group but not in the PLA-group (p < 0.01; es = 1.17). The high frequency power of the HRV spectrum had already improved by the second week (p < 0.01; es = 1.13) and remained elevated until the last week of intervention (p < 0.01; es = 1.43). The same positive results were described in 6MWT distance (p = 0.04; es = 0.39) and the change (∆) of heart rate recovery (HRR) from 1 min (p = 0.02; es = 0.68).

Conclusion

IMT increases HRV, improves 6MWT distance and HRR.



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Academy News – March PM&R Journal

As the primary medical society for the specialty of PM&R, your Academy is focused on moving the specialty and you forward. Academy membership supports initiatives to assist our members with:

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Information for Authors



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Table of Contents



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Instrumental Variables: Uses and Limitations

Observational studies are limited by the issue of confounding. For example, light-to-moderate drinkers tend to have lower risk of cardiovascular disease than nondrinkers. This association could be due to a causal effect of alcohol on the body, or it could be due to other attributes of light-to-moderate drinkers, such as high socioeconomic status or the ability to practice moderation across a range of behaviors. Statistical adjustment only imperfectly addresses confounding [1]: Confounders such as socioeconomic status may be crudely measured, resulting in residual confounding; plus, some confounders—such as intangible attributes like the ability to practice moderation—may remain unmeasured.

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Copyright Page



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Editorial Board



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Spanish Translated Abstracts



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Russian Doll Genes and Complex Chromosome Rearrangements in Oxytricha trifallax

Ciliates have two different types of nuclei per cell, with one acting as a somatic, transcriptionally active nucleus (macronucleus; abbr. MAC) and another serving as a germline nucleus (micronucleus; abbr. MIC). Furthermore, Oxytricha trifallax undergoes extensive genome rearrangements during sexual conjugation and post-zygotic development of daughter cells. These rearrangements are necessary because the precursor MIC loci are often both fragmented and scrambled, with respect to the corresponding MAC loci. Such genome architectures are remarkably tolerant of encrypted MIC loci, because RNA-guided processes during MAC development reorganize the gene fragments in the correct order to resemble the parental MAC sequence. Here, we describe the germline organization of several nested and highly scrambled genes in Oxytricha trifallax. These include cases with multiple layers of nesting, plus highly interleaved or tangled precursor loci that appear to deviate from previously described patterns. We present mathematical methods to measure the degree of nesting between precursor MIC loci, and revisit a method for a mathematical description of scrambling. After applying these methods to the chromosome rearrangement maps of O. trifallax we describe cases of nested arrangements with up to five layers of embedded genes, as well as the most scrambled loci in O. trifallax.



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The Use of Nerve Transfers to Restore Upper Extremity Function in Cervical Spinal Cord Injury

Nerve transfer surgery to restore upper extremity (UE) function in cervical spinal cord injury (SCI) is novel and may transform treatment. Determining candidacy even years post-SCI is ill-defined and deserves investigation.

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Herpesvirus-encoded microRNAs detected in human gingiva alter host cell transcriptome and regulate viral infection

Publication date: Available online 15 March 2018
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms
Author(s): Afsar R. Naqvi, Alexandra Seal, Jennifer Shango, Maria Brambila Navarette, Gloria Martinez, Gabriela Chapa, Shirin Hasan, Tejabhiram Yadavalli, Dinesh Jaishankar, Deepak Shukla, Salvador Nares
MicroRNAs (miRNAs) are small, non-coding RNAs of ~18-25 nucleotides that have gained extensive attention as critical regulators in complex gene networks including immune cell lineage commitment, differentiation, maturation, and maintenance of immune homeostasis and function. Many viruses encode miRNAs that directly downregulate the expression of factors of the innate immune system, which includes proteins involved in promoting apoptosis and recruitment. In this study, we examined the expression profiles of three previously identified viral miRNAs (v-miRs) from the human herpesvirus (HHV) family, HSV-1 (miR-H1), KSHV (miR-K12-3-3p), and HCMV (miR-US4) in healthy and diseased periodontal tissues and observed increased levels of v-miRs in diseased tissues. To understand the significance of this increase, we overexpressed v-miRs in human oral keratinocytes (HOK), a common target for various HHV, and analyzed the impact of miR-H1 and miR-K12-3-3p on the host transcriptome. More than 1300 genes were altered in HOK overexpressing miR-H1 and miR-K12-3-3p. Global pathway analysis of deregulated genes identified several key cellular pathways that may favor viral persistence. Using bioinformatic analysis, we predicted hundreds of potential v-miR binding sites on genes downregulated by miR-H1 and miR-K12-3-3p and validated three novel target v-miR sites suggesting widespread direct and indirect modualtion of numerous host genes/pathways by a single v-miR. Finally, in vitro HSV-1 infection assays showed that miR-H1 can regulate viral entry and infection in human oral keratinocytes (HOK). Overall, our results demonstrate clinical and functional relevance of pathogenic viral molecules viz., v-miRs that regulate both host and viral functions and may contribute to the pathogenesis of inflammatory oral diseases.



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Direct-acting Antivirals Response in an Acute Nosocomial Genotype 1b HCV Outbreak



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Long-term outcome of transjugular intrahepatic portosystemic shunt for portal hypertension in autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD) with congenital hepatic fibrosis (CHF) causes portal hypertension and its complications. A transjugular intrahepatic portosystemic shunt (TIPSS) could serve as a symptomatic treatment for portal hypertension-related symptoms in these children.

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Is it time to include non-alcoholic fatty liver disease in the current risk scores for atrial fibrillation?



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Direct-acting Antivirals Response in an Acute Nosocomial Genotype 1b HCV Outbreak



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Long-term outcome of transjugular intrahepatic portosystemic shunt for portal hypertension in autosomal recessive polycystic kidney disease

Autosomal recessive polycystic kidney disease (ARPKD) with congenital hepatic fibrosis (CHF) causes portal hypertension and its complications. A transjugular intrahepatic portosystemic shunt (TIPSS) could serve as a symptomatic treatment for portal hypertension-related symptoms in these children.

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Is it time to include non-alcoholic fatty liver disease in the current risk scores for atrial fibrillation?



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Screening for Chlamydia, Gonorrhea, and High-Risk Sexual Behaviors in Utah's Juvenile Justice Population: Results and Implications for Practice

Compared with adults, sexually active adolescents are at higher risk of acquiring chlamydia and gonorrhea (CT/GC). Additionally, sex trafficking and sexual violence are serious public health problems. Before this project, no data on the sexual behaviors of adolescents within Utah's Juvenile Justice System had been gathered in a systematic manner that provided a population-based perspective.From July 1, 2015, through December 30, 2016, nurses and staff in 18 Utah Juvenile Justice facilities screened all youth admitted to their facilities.

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Long Noncoding RNA GAPLINC Promotes Cells Migration and Invasion in Colorectal Cancer Cell by Regulating miR-34a/c-MET Signal Pathway

Abstract

Background

Gastric adenocarcinoma predictive long intergenic noncoding RNA (GAPLINC) has been detected in colorectal cancer (CRC) cells and reportedly performs many functions related to tumor proliferation and metastasis. Aim The present study aimed to comprehensively explore the biological functions of GAPLINC and their underlying mechanism in CRC cell.

Methods

The human cancer LncRNA PCR array was used to detect the differentially expressed long noncoding RNAs in human CRC samples. Real-time PCR, dual-luciferase assay, RNA pull-down assay, Transwell assay, and western blot analysis were performed to explore the molecular mechanism underlying GAPLINC functions related to migration and invasion of a human CRC cell line (HCT116).

Results

Compared to the non-cancerous tissues, GAPLINC expression was obviously increased in CRC tissues. In HCT116, silencing of GAPLINC weakened cell migration and invasion, while overexpression of GAPLINC significantly promoted cell migration and invasion. Through dual-luciferase, RNA pull-down, and Transwell assays, we verified that miR-34a was the downstream molecule of GAPLINC and that miR-34a negatively regulated the migration and invasion of HCT116 cell. Furthermore, we found that GAPLINC positively regulated the miR-34a target gene c-MET in CRC tissues.

Conclusions

Our findings revealed that GAPLINC was up-regulated in CRC tissues and was involved in the migration and invasion of CRC cells by regulating miR-34a/c-MET signaling pathway.



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Comparison of the Effects of Vonoprazan and Lansoprazole for Treating Endoscopic Submucosal Dissection-Induced Artificial Ulcers

Abstract

Background

Vonoprazan exhibits a more potent, rapid, and longer-lasting inhibitory effect on gastric acid secretion than proton pump inhibitors; however, whether it is more effective than PPI for treating endoscopic submucosal dissection (ESD)-induced artificial ulcers remains controversial.

Aim

This study aimed to assess and compare the effects of vonoprazan and lansoprazole for treating ESD-induced artificial ulcers.

Methods

This prospective, randomized controlled trial enrolled 149 patients who underwent ESD for the treatment of early gastric neoplasms from April 2015 to May 2017. They were randomly treated with either 20 mg/day vonoprazan (V group) or 30 mg/day lansoprazole (L group) orally. The primary end points were the area and shrinkage ratio of the ulcers at 4 and 8 weeks post-ESD.

Results

Data from 127 patients were analyzed, which showed that the 4- and 8-week healing ratios were not significantly different between the V and L groups (4 weeks, 16.3 vs. 25.8%; 8 weeks, 86.9 vs. 90.9%, respectively). Similarly, the shrinkage ratio, categorized as less than 90%, 90% or more but less than 100%, or 100% at 4 weeks and as less than 100% or 100% at 8 weeks were not statistically different between the V and L groups (4 weeks: 12, 41, 8 vs. 13, 41, 12, p = 0.7246; 8 weeks: 9, 52 vs. 9, 57, p = 0.8568). Delayed bleeding was also not significantly different between both the groups (5.4 vs. 5.3%; p = 0.9844).

Conclusions

Vonoprazan is as effective as lansoprazole in treating ESD-induced ulcers.



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A Tribute to Paul H. Guth, MD (1927–2017)



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An Analysis of the Clinical, Laboratory, and Histological Features of Striped, Punctate, and Nodular Gastric Antral Vascular Ectasia

Abstract

Background

Gastric antral vascular ectasia (GAVE) commonly presents as linear striped ("watermelon stomach") or punctate phenotypes, to which a newly discovered nodular form was recently added.

Aims

We performed a retrospective cohort study to detail and compare the clinical and histological characteristics of major GAVE phenotypes.

Methods

In 136 GAVE patients (tertiary care ambulatory and inpatient, median age 61.3 years, 73 men, and 63 women), clinical and laboratory results were recorded, with comorbidities, endoscopy indications, and complications of cirrhosis. In 74 patients, GAVE histopathology was cataloged by a pathologist masked to endoscopy results.

Results

Median age 61.3 years, 73 men, and 63 women. GAVE phenotypes were: linear striped—62 (46%), punctate—32 (24%), and nodular—41 (30%). Endoscopy was commonly performed for variceal screening in linear striped (45%) and nodular (34%) GAVE and for gastrointestinal bleeding in punctate (41%) and nodular (29%) GAVE, respectively. Of 89 cirrhotic patients, 37.5% each had linear striped or nodular GAVE, 24.7% had punctate forms (p = 0.03). Child–Turcotte–Pugh and Model for End-Stage Liver Disease scores were similar among phenotypes. Histologically, reactive epithelial hyperplasia and vascular ectasia were universal; smooth muscle proliferation was more common and consistent (78–86%) than microvascular thrombi (27–59%) and fibrohyalinosis (18–53%), which each varied with phenotype.

Conclusions

Nodular GAVE is a gastric mucosal abnormality that is similar to the linear striped and punctate phenotypes, yet has distinct clinical and histological features. Increased awareness of nodular GAVE by endoscopists is needed to avoid its misdiagnosis as nonspecific antral nodules.



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Effect of Bifidobacterium infantis 35624 (Align) on the Lactulose Breath Test for Small Intestinal Bacterial Overgrowth

Abstract

Background

Small intestinal bacterial overgrowth (SIBO) may cause symptoms in patients with abdominal bloating, distension, and gas. SIBO can be assessed using the lactulose breath test (LBT). A commonly used probiotic supplement is Align containing Bifidobacterium infantis 35624. The aim of this study was to determine the effect of B. infantis 35624 on hydrogen and methane excretion during LBT.

Methods

Healthy subjects underwent LBT before and after 2 weeks of daily Align administration. Hydrogen and methane concentrations were measured for each breath sample. Results are expressed as mean ± SE and analyzed using repeated measures ANCOVA. A breath test was considered positive if hydrogen and/or methane increased > 20 ppm above baseline by 90 min of the test or if a dual hydrogen peak was present.

Results

Nineteen healthy subjects were studied. Hydrogen levels were similar pre- and post-probiotic across the 3-h study (p = 0.768). In contrast, methane levels were significantly higher with probiotic administration (p = 0.012). A rise in methane > 20 ppm was seen in three subjects pre-probiotic but six post-probiotic. Of the 19 subjects, an "abnormal" LBT pre-probiotic was present in ten subjects and during the probiotic, 13 were abnormal.

Conclusions

This study found that 2 weeks of B. infantis 35624 (Align) supplementation affects LBT assessment for SIBO by significantly increasing methane, but not hydrogen, excretion after lactulose administration. Methane levels reached values that would be considered positive for SIBO patients. This study suggests that patients undergoing LBT should discontinue probiotics prior to the test as these supplements may alter the test results.



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Autophagy Strengthens Intestinal Mucosal Barrier by Attenuating Oxidative Stress in Severe Acute Pancreatitis

Abstract

Background

Intestinal mucosal barrier dysfunction can be caused by severe acute pancreatitis (SAP). It is normally associated with changes to mucosal autophagy and oxidative stress.

Objective

The aim of this study was to investigate the correlation between autophagy and oxidative stress on the intestinal mucosal barrier of SAP rat model.

Methods

SAP was induced by retrograde injection of sodium taurocholate (5%) into the biliopancreatic duct. Bacterial translocation (BT) was detected by 16S rDNA sequencing analysis. Morphological alterations in the pancreas and gut were determined by hematoxylin–eosin staining. Oxidative stress status was determined by measuring the level of intestinal malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx). Western blot, RT-PCR, and immunofluorescent staining were preformed to analyze the expression of tight junction and autophagy proteins.

Results

According to the sequencing analysis, rats in SAP group were divided into BT (+) group (n = 9) and BT (−) group (n = 8). Pancreatic and intestinal injuries in SAP group were significantly higher than sham operation group. The content of MDA was clearly elevated, and SOD as well as GPx activities were decreased in BT (+) group as compared with BT (−) group. The expression of LC3II and Beclin1 in BT (−) group was higher than that observed in BT (+). In contrast, BT (+) group had a higher level of claudin-2 and a lower level of zonula occluden-1, occludin, and claudin-1.

Conclusion

These results suggest that activated autophagy may attenuate intestinal mucosal barrier dysfunction by preventing and reducing the oxidative stress in SAP.



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Crohn’s Disease in Niemann–Pick Disease Type C1: Caught in the Cross-Fire of Host-Microbial Interactions



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Non-evidence-Based Medicine: The Gastroenterologist’s Role and Responsibility



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Concise Commentary: Presurgical Evaluation of IPMNs—Eight Is Enough



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Acetarsol Suppositories: Effective Treatment for Refractory Proctitis in a Cohort of Patients with Inflammatory Bowel Disease

Abstract

Background

Management of proctitis refractory to conventional therapies presents a common clinical problem. The use of acetarsol suppositories, which are derived from organic arsenic, was first described in 1965. Data concerning clinical efficacy and tolerability are very limited.

Aim

To examine the efficacy of acetarsol suppositories for the treatment of refractory proctitis.

Methods

A retrospective analysis was performed on patients with inflammatory bowel disease treated with acetarsol suppositories between 2008 and 2014 at Addenbrooke's Hospital, Cambridge, United Kingdom. Clinical response was defined as resolution of symptoms back to baseline at the time of next clinic review.

Results

Thirty-nine patients were prescribed acetarsol suppositories between March 2008 and July 2014 (29 patients with ulcerative colitis, nine with Crohn's disease, and one with indeterminate colitis). Thirty-eight were included for analysis. The standard dose of acetarsol was 250 mg twice daily per rectum for 4 weeks. Clinical response was observed in 26 patients (68%). Of the 11 patients who had endoscopic assessment before and after treatment, nine (82%) showed endoscopic improvement and five (45%) were in complete remission (Wilcoxon signed-rank test p = 0.006). One patient developed a macular skin rash 1 week after commencing acetarsol, which resolved within 4 weeks of drug cessation.

Conclusion

Acetarsol was effective for two out of every three patients with refractory proctitis. This cohort had failed a broad range of topical and systemic treatments, including anti-TNFα therapy. Clinical efficacy was reflected in significant endoscopic improvement. Adverse effects of acetarsol were rare.



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Gastric Acid and Enteric Infections: Souring on the Use of PPIs



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A 19-Gauge Histology Needle Versus a 19-Gauge Standard Needle in Endoscopic Ultrasound-Guided Fine-Needle Aspiration for Solid Lesions: A Multicenter Randomized Comparison Study (GREATER Study)

Abstract

Background

The necessity of histological analysis is increasing. A 19-gauge histology needle (PC19) in endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has recently been developed and has shown high yields of tissue acquisition and histological diagnosis.

Aims

To compare the histological diagnostic yield in single-pass EUS-FNA for solid lesions using PC19 and a standard 19-gauge needle (EC19).

Patients and Methods

Consecutive patients with solid lesions were enrolled and underwent one pass with each of PC19 and EC19 for EUS-FNA with the randomized order of the needles. The primary endpoint was the histological diagnostic accuracy. The secondary endpoints were the feasibility, yield of histological core, cytological and overall diagnostic accuracies, and adverse events. Subgroup analysis was performed for the optimal situation with PC19.

Results

Of the 115 patients, 110 underwent EUS-FNA and five were excluded. EUS-FNA was performed from the esophagus in four, stomach in 80, or duodenum in 26. The final diagnosis was malignancy in 100 and benign in 10. The feasibility was 98.2 and 97.3% with PC19 and EC19, respectively (p = 1.00). The rate of presence of a histological core and the histological, cytological, and overall diagnostic accuracies for PC19 versus EC19 were 84.6 versus 80.9% (p = 0.593), 83.6 versus 73.6% (p = 0.099), 63.6 versus 56.4% (p = 0.335), and 90.0 versus 79.1% (p = 0.039), respectively. PC19 was favored in the trans-esophageal/gastric approaches to obtain a histological diagnosis (p = 0.013). Adverse events were observed in four patients.

Conclusion

Single-pass EUS-FNA with PC19 was feasible and showed significantly higher overall diagnostic accuracy and an increased tendency towards histological diagnostic accuracy, especially with trans-esophageal/gastric FNA.



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Profiles: Benjamin Lebwohl, MD, MS



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Plastic Surgery: Cholangioscopic Intra-stent Balloon Retrieval of a Proximally Migrated Biliary Stent



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Novel Albumin–Bilirubin Grade-Based Risk Prediction Model for Patients with Hepatocellular Carcinoma Undergoing Chemoembolization

Abstract

Background

Recently, albumin–bilirubin (ALBI) grade has been suggested as a better surrogate for hepatic functional reserve for patients with hepatocellular carcinoma (HCC).

Aims

We developed and validated a novel prediction model to predict outcome for HCC patients who underwent transcatheter arterial chemoembolization (TACE) as a first-line therapy.

Methods

From a multivariate Cox regression model for overall survival, five objective variables (ALBI grade), the Barcelona clinic liver cancer (BCLC) stage, response after the first TACE session, Alpha-fetoprotein level, and sex were chosen and the ABRAS score was developed from the derivation cohort (n = 476) and scored to generate an 8-point risk prediction model. The model's prognostic performance was assessed in the randomly assigned internal validation set (n = 475) and external validation set (n = 243).

Results

The ALBI grade was able to stratify patient survival within the same Child–Pugh class. The time-dependent area under receiver operating characteristics curves (AUROCs) for overall survival at 1 and 3 years were 0.78 and 0.73 in the training set, 0.78 and 0.71 in the internal validation set, and 0.70 and 0.65 in the external validation set, respectively. When stratified by BCLC stage, ABRAS score at a cutoff point of more than 3, 4, and 5 for BCLC stage 0/A, B, and C could identify subset of patients with dismal prognosis.

Conclusion

ABRAS score was useful in estimating prognosis for patients who underwent TACE as a first-line therapy. This score can be useful in planning and guiding treatment strategies with TACE, which warrants prospective validation.



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Role of Esophageal Metal Stents Placement and Combination Therapy in Inoperable Esophageal Carcinoma: A Systematic Review and Meta-analysis

Abstract

Introduction

More than 50% of patients with esophageal cancer already have inoperable disease at the time of diagnosis. Controversy surrounds the outcomes of patients with advanced esophageal cancer who receive palliative care by either stent alone or stent plus an additional modality. We set out to perform a systematic review and meta-analysis of studies assessing the use of metal stents as treatment options for symptomatic improvement, survival, and adverse events.

Methods

We searched Embase, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception until January 14, 2016, as well as other databases for randomized controlled trials (RCTs) comparing esophageal stent versus either esophageal stent plus brachytherapy, radiotherapy, or chemotherapy. For quality assurance purposes throughout the systematic review, multiple independent extractions were performed, and the process was executed as per the standards of the Cochrane collaboration. Primary outcomes were mean change in dysphagia score, overall survival, and quality of life. Secondary outcomes were adverse events including fever, severe pain, aspiration, fistula, stent migration, perforation, and restenosis.

Results

Eight RCTs enrolling 732 patients were included with three distinct comparisons: stents combination therapy vs stents alone (5 studies, n = 417), stents alone versus brachytherapy alone (2 studies, n = 274), and stents + brachytherapy vs brachytherapy alone (1 study, n = 41). Stents combination therapy was defined as stents plus radiotherapy, chemotherapy, or both. Mean change in dysphagia scores favored stents combination therapy versus stents alone, and the effect was seen in patients surviving longer than 3 months. Stents combination therapy was also associated with a more favorable overall survival. The risks of stent migration, aspiration pneumonia, and restenosis were lower in the stents combination group compared to stents alone, while the risks of severe pain, hemorrhage, and fistula formation were higher. Changes in dysphagia scores and overall survival did not differ significantly in the brachytherapy-alone vs stents-alone comparison. The risk of fistula formation and hemorrhage were higher in the stents-alone group, while the risk of perforation was lower, compared to brachytherapy alone. Quality of life improvements were seen in all treatment groups, but were not pooled in analysis due to differing methods of measurement.

Discussion

While there appears to be no immediate short-term differences, those who live longer than 3 months experience a significant improvement in dysphagia score using a stents combination therapy approach vs stents alone. The combination therapy significantly improves the overall survival as well as showed improvements in quality of life scores. Larger randomized controlled trials are needed to assess improvements in dysphagia score, overall survival, quality of life, and adverse events.



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Clinicopathology and Survival in Patients with Gastroesophageal Reflux After Radical Surgery of Proximal Gastric Cancer

Abstract

Background

Gastroesophageal reflux (GR) after radical resection of proximal gastric cancer (PGC) may influence survival; however, few studies have investigated survival in PGC patients who develop GR following radical resection. This study aimed to correlate the occurrence of GR after proximal gastrectomy (PG) and total gastrectomy (TG) with clinicopathological factors and long-term survival.

Methods

The PGC patient cohort was retrospectively grouped as follows: postoperative patients with and without GR (NGR). Clinicopathological characteristics and survival data were compared between the two groups.

Results

A total of 88 patients who underwent PG (53%) experienced postoperative GR; however, only 30 patients who underwent TG (14%) experienced GR (P = 0.000). The incidence of GR was significantly associated with surgical procedure (P < 0.01), tumor size (P < 0.01), infiltration depth (P < 0.01), lymph node metastasis (P = 0.018), postoperative distant metastasis (P < 0.01) and recurrence (P = 0.001). The 5-year overall survival of the GR group was significantly worse than that of the NGR group (39.3 vs. 46.5%, respectively; P = 0.046). The PG and TG groups had significantly different 5-year overall survival (45.2 vs. 50.9%, respectively; P = 0.047), and multivariate analysis revealed GR as an independent risk factor associated with poor overall survival.

Conclusions

Patients who experienced GR after radical resection for PGC were more likely to develop recurrence and metastasis, leading to shorter survival. TG for PGC was associated with a more favorable 5-year overall survival than was PG. Thus, TG should be performed for PGC patients with tumors larger than 5 cm, T3/T4 disease or lymph node metastasis to improve their long-term survival.



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Potential Impact of Helicobacter Pylori on Hepatic Encephalopathy Pathophysiology



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Accelerated Step-Up Infliximab Use Is Associated with Sustained Primary Response in Pediatric Crohn’s Disease

Abstract

Background

Earlier introduction of infliximab (IFX) in Crohn's disease (CD) may be associated with a sustained remission.

Methods and Aims

Children on scheduled IFX therapy for predominant luminal CD after successful induction (drop in PCDAI by ≥ 15) and a minimum of 2-year IFX follow-up were included. We compared outcomes of children treated with early (within 3 months from diagnosis) versus later IFX (after failing conventional therapy ≥ 3 months) and identify clinical predictors of sustained primary response (SPR) in our cohort. SPR was defined as CS-free clinical remission without requiring IFX dose escalation and/or surgical excision and/or switch to second anti-TNFs due to LOR or allergic reaction.

Results

Sixty-four children received IFX therapy for CD during the study period. Forty-three children on scheduled IFX therapy for luminal CD met the inclusion criteria. During the median follow-up of 3.05 years (IQR 2.6–3.5 years), SPR was observed in 17/43 (40%). SPR was associated with shorter time from diagnosis to the initiation of IFX (5.4 vs. 18.7 months, p = 0.006). Binary logistic regression using multiple variables also confirmed that only early use of IFX is associated with SPR.

Conclusion

Early step-up use of IFX in children with CD with inadequate clinical response to conventional therapies leads to sustained primary response over 2 years.



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Paramedic - Multiple Locations - Arcadian Ambulance

Acadian provides emergency and non-emergency transports to 72 parishes/counties in Louisiana, Texas, and Mississippi, and is the largest privately-owned EMS service in the country. In addition, Acadian is employee-owned and nationally accredited in every market we serve. Our 4,000+ employees are committed to quality patient care and customer service. In business for 40+ years and only growing stronger ...

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Staff Nurse – Vitalink - New Hanover Regional Medical Center

Staff Nurse – Vitalink The Staff RN provides high quality patient care and safe medical transport to sick and injured patients in all age groups. Essential Responsibilities: Collaborates with team and initiates care plan based on patient assessment and significant other input/data. Continuously reviews and revises plan as needed per patient's condition. Maintains thorough patient care documentation ...

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Critical Care Transport Paramedic – Vitalink - New Hanover Regional Medical Center

Critical Care Transport Paramedic – Vitalink Essential Responsibilities: Provides high quality patient care and safe medical transport to sick and injured patients in all age groups Uses an interdisciplinary model to work with the Airlink/Vitalink Staff Nurse and other appropriate medical personnel to establish and prioritize a plan of care consistent with approved treatment protocols, policies ...

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Natural antioxidants in prevention of accelerated ageing: a departure from conventional paradigms required

Abstract

The modern lifestyle is characterised by various factors that cause accelerating ageing by the upregulation of oxidative stress and inflammation—two processes that are inextricably linked in an endless circle of self-propagation. Inflammation in particular is commonly accepted as aetiological factor in many chronic disease states, such as obesity, diabetes and depression. In terms of disease prevention or treatment, interventions aimed at changing dietary and/or exercise habits have had limited success in practise, mostly due to poor long-term compliance. Furthermore, other primary stimuli responsible for eliciting an oxidative stress or inflammatory response—e.g. psychological stress and anxiety—cannot always be easily addressed. Thus, preventive medicine aimed at countering the oxidative stress and/or inflammatory responses has become of interest. Especially in developing countries, such as South Africa, the option of development of effective strategies from plants warrants further investigation. A brief overview of the most relevant and promising South African plants which have been identified in the context of inflammation, oxidative stress and chronic disease is provided here. In addition, and more specifically, our group and others have shown considerable beneficial effects across many models, after treatment with products derived from grapes. Of particular interest, specific cellular mechanisms have been identified as therapeutic targets of grape-derived polyphenols in the context of inflammation and oxidative stress. The depth of these studies afforded some additional insights, related to methodological considerations pertaining to animal vs. human models in natural product research, which may address the current tendency for generally poor translation of positive animal model results into human in vivo models. The importance of considering individual data vs. group averages in this context is highlighted.



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Protective effect of the total flavonoids from Apocynum venetum L. on carbon tetrachloride-induced hepatotoxicity in vitro and in vivo

Abstract

Apocynum venetum L., belonging to the family Apocynaceae, is a popular medicinal plant, which is commonly used in the treatment of hypertension, neurasthenia, and hepatitis in China. In the present study, the total flavonoids (TFs) were prepared from the leaves of A. venetum, and its protective effects on carbon tetrachloride (CCl4)-induced hepatotoxicity in a cultured HepG2 cell line and in mice were investigated. Cell exposed to 0.4% CCl4 (v/v) for 6 h led to a significant decrease in cell viability, increased LDH leakage, and intracellular reactive oxygen species (ROS). CCl4 also induced cell marked apoptosis, which was accompanied by the loss of mitochondrial membrane potential (MMP). Pretreatment with TFs at concentrations of 25, 50, and 100 μg/mL effectively relieved CCl4-induced cellular damage in a dose-dependent manner. In vivo, TFs (100, 200, and 400 mg/kg BW) were administered via gavage daily for 14 days before CCl4 treatment. The high serum ALT and AST levels induced by CCl4 were dose-dependently suppressed by pretreatment of TFs (200 and 400 mg/kg BW). Histological analysis also supported the results obtained from serum assays. Furthermore, TFs could prevent CCl4-caused oxidative damage by decreasing the MDA formation and increasing antioxidant enzymes (CAT, SOD, GSH-Px) activities in liver tissues. In summary, both in vitro and in vivo data suggest that TFs, prepared from A. venetum, showed a remarkable hepatoprotective and antioxidant activity against CCl4-induced liver damage.



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The biting performance of Homo sapiens and Homo heidelbergensis

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Publication date: May 2018
Source:Journal of Human Evolution, Volume 118
Author(s): Ricardo Miguel Godinho, Laura C. Fitton, Viviana Toro-Ibacache, Chris B. Stringer, Rodrigo S. Lacruz, Timothy G. Bromage, Paul O'Higgins
Modern humans have smaller faces relative to Middle and Late Pleistocene members of the genus Homo. While facial reduction and differences in shape have been shown to increase biting efficiency in Homo sapiens relative to these hominins, facial size reduction has also been said to decrease our ability to resist masticatory loads. This study compares crania of Homo heidelbergensis and H. sapiens with respect to mechanical advantages of masticatory muscles, force production efficiency, strains experienced by the cranium and modes of deformation during simulated biting. Analyses utilize X-ray computed tomography (CT) scan-based 3D models of a recent modern human and two H. heidelbergensis. While having muscles of similar cross-sectional area to H. heidelbergensis, our results confirm that the modern human masticatory system is more efficient at converting muscle forces into bite forces. Thus, it can produce higher bite forces than Broken Hill for equal muscle input forces. This difference is the result of alterations in relative in and out-lever arm lengths associated with well-known differences in midfacial prognathism. Apparently at odds with this increased efficiency is the finding that the modern human cranium deforms more, resulting in greater strain magnitudes than Broken Hill when biting at the equivalent tooth. Hence, the facial reduction that characterizes modern humans may not have evolved as a result of selection for force production efficiency. These findings provide further evidence for a degree of uncoupling between form and function in the masticatory system of modern humans. This may reflect the impact of food preparation technologies. These data also support previous suggestions that differences in bite force production efficiency can be considered a spandrel, primarily driven by the midfacial reduction in H. sapiens that occurred for other reasons. Midfacial reduction plausibly resulted in a number of other significant changes in morphology, such as the development of a chin, which has itself been the subject of debate as to whether or not it represents a mechanical adaptation or a spandrel.



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An Investigation into the Recent Increase in Gastric Cancer in the USA

Abstract

Background

The USA has among the lowest gastric cancer incidence rates worldwide.

Aim

To investigate whether increasing immigration from high cancer incidence countries has altered the GC incidence in a large US metropolitan area.

Methods

This was a retrospective cohort study among an underprivileged, multiethnic population in Texas. Gastric cancer cases diagnosed during 2005–2015 were identified using the cancer registry of the public medical care system for Harris County. All cases were histologically confirmed; demographic and clinical data were obtained from review of electronic medical records. Census data were used to determine the distribution of the adult county population by race/ethnicity and age. Two time periods (2005–2009 and 2010–2015) were studied to correspond with census reporting intervals.

Results

In total, 299 cases were included: average age 55 years, 59% males and 63% Hispanics (predominantly recent immigrants of Central-American origin). The gastric cancer incidence remained stable among non-Hispanic Whites and Blacks but increased significantly among Hispanics (from 10 to 17 cases/100,000 persons/year, RR = 2.0, 95% CI 1.4–2.5, p = 0.001). Among Hispanics, gastric cancer incidence rose significantly among persons aged 40–59 years and ≥ 60 years and was likely to be at advanced stage at the time of diagnosis even in the younger age population.

Conclusion

Gastric cancer incidence significantly increased among Hispanics residing in Houston resulting in changes in gastric cancer incidence becoming more unevenly experienced across the US population. Consideration should be given to gastric cancer preventive efforts, especially among immigrant populations from high gastric cancer risk countries.



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Subtypes of the Type II Pit Pattern Reflect Distinct Molecular Subclasses in the Serrated Neoplastic Pathway

Abstract

Background

Colorectal serrated lesions (SLs) are important premalignant lesions whose clinical and biological features are not fully understood.

Aims

We aimed to establish accurate colonoscopic diagnosis and treatment of SLs through evaluation of associations among the morphological, pathological, and molecular characteristics of SLs.

Methods

A total of 388 premalignant and 18 malignant colorectal lesions were studied. Using magnifying colonoscopy, microsurface structures were assessed based on Kudo's pit pattern classification system, and the Type II pit pattern was subcategorized into classical Type II, Type II-Open (Type II-O) and Type II-Long (Type II-L). BRAF/KRAS mutations and DNA methylation of CpG island methylator phenotype (CIMP) markers (MINT1, − 2, − 12, − 31, p16, and MLH1) were analyzed through pyrosequencing.

Results

Type II-O was tightly associated with sessile serrated adenoma/polyps (SSA/Ps) with BRAF mutation and CIMP-high. Most lesions with simple Type II or Type II-L were hyperplastic polyps, while mixtures of Type II or Type II-L plus more advanced pit patterns (III/IV) were characteristic of traditional serrated adenomas (TSAs). Type II-positive TSAs frequently exhibited BRAF mutation and CIMP-low, while Type II-L-positive TSAs were tightly associated with KRAS mutation and CIMP-low. Analysis of lesions containing both premalignant and cancerous components suggested Type II-L-positive TSAs may develop into KRAS-mutated/CIMP-low/microsatellite stable cancers, while Type II-O-positive SSA/Ps develop into BRAF-mutated/CIMP-high/microsatellite unstable cancers.

Conclusions

These results suggest that Type II subtypes reflect distinct molecular subclasses in the serrated neoplasia pathway and that they could be useful hallmarks for identifying SLs at high risk of developing into CRC.



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Eliminating Dietary Gluten: Don’t Be a “Glutton for Punishment”



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Retreatment Efficacy of Sofosbuvir/Ombitasvir/Paritaprevir/Ritonavir + Ribavirin for Hepatitis C Virus Genotype 4 Patients

Abstract

Background

The current standard of care for patients with chronic hepatitis C virus (HCV) infection is a combination of direct-acting antiviral agents (DAAs). However, rare clinical trials have been reported on the combination regimen of sofosbuvir (SOF) with ombitasvir, paritaprevir, and ritonavir (OBV/PTV/r) plus ribavirin (RBV) for treated patients with HCV genotype 4 (GT4) infection.

Aims

To clarify the retreatment efficacy and safety of the recent regimen, SOF with OBV/PTV/r + RBV, for chronic HCV GT4-experienced patients who failed treatment with DAA-based regimens.

Methods

A total of 113 treatment-experienced patients were allocated for the completion of their treatment period. The enrolled patients were treated orally with SOF plus a fixed dose combination of OBV/PTV/r + RBV, which was administered orally based on the patients' tolerability. The primary end point was a sustained virological response (HCV RNA < 15 IU/mL), observed 12 weeks after the end of the treatment (SVR12).

Results

Among all patients, the treatment-experienced patients with SOF plus OBV/PTV/r + RBV had a higher SVR12 rate (97%; 109/113). Further, SVR12 was achieved by 98% (81/83) of non-cirrhotic patients and 93% (28/30) of cirrhotic patients. Additionally, the most common adverse events reported included fatigue, headache, insomnia, nausea, and dyspnea.

Conclusions

The recent multi-targeted regimen of SOF plus OBV/PTV/r + RBV was well tolerated and achieved excellent SVR rates among retreatment-experienced Egyptian patients with prior DAA treatments failure, thus providing an alternative regimen for the retreatment of difficult-to-cure HCV GT4 patients.



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Evolving Models of Rehabilitation-Related Patient Safety and Quality: PIECES

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Publication date: Available online 14 March 2018
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Bruce M. Gans




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PWW Media, Inc. announces all new HIPAA training solution for EMS

MECHANICSBURG, PA — PWW Media, Inc, the Nation's leading resource in EMS compliance, has unveiled the latest HIPAA training solution for the EMS industry – HIPAA TV 2.0. HIPAA TV 2.0 is an all-new, interactive program, specifically designed for EMS and ambulance industry professionals – including practitioners, administrators, and revenue cycle staff. The program targets new ...

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Beetroot supplementation improves the physiological responses to incline walking

Abstract

Purpose

We investigated the effects of an acute 24-h nitrate-rich beetroot juice supplement (BR) on the energy cost, exercise efficiency and blood pressure responses to intermittent walking at different gradients.

Methods

In a double-blind, cross-over design, eight participants were provided with a total of 350 ml of nitrate-rich (~ 20.5 mmol nitrate) BR or placebo (PLA) across 24 h before completing intermittent walking at 3 km/h on treadmill at gradients of 1, 5, 10, 15 and 20%.

Results

Resting mean arterial pressure (MAP) was ~ 4.1% lower after BR (93 vs. 89 mmHg; P = 0.001), as well as during exercise (102 vs. 99 mmHg; P = 0.011) and recovery (97 vs. 94 mmHg; P = 0.001). Exercising (1227 vs. 1129 ml/min P < 0.001) and end-stage (1404 vs. 1249 ml/min; P = 0.002) oxygen uptake ( \(\dot {V}\) O2) was lower in BR compared to PLA, which was accompanied by an average reduction in phase II \(\dot {V}\) O2 amplitude (1067 vs. 940 ml/min; P = 0.025). Similarly, recovery \(\dot {V}\) O2 (509 vs. 458 ml/min; P = 0.001) was lower in BR. Whole blood potassium concentration increased from pre-post exercise in PLA (4.1 ± 0.3 vs. 4.5 ± 0.3 mmol/L; P = 0.013) but not BR (4.1 ± 0.31 vs. 4.3 ± 0.2 mmol/L; P = 0.188).

Conclusions

Energy cost of exercise, recovery of \(\dot {V}\) O2, MAP and blood markers were ameliorated after BR. Previously-reported mechanisms explain these findings, which are more noticeable during less-efficient walking at steep gradients (15–20%). These findings have practical implications for hill-walkers.



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Mucosal Impedance Measurements Differentiate Pediatric Patients with Active vs Inactive Eosinophilic Esophagitis

Background & Aims: Eosinophilic esophagitis (EoE) is a chronic disorder in children that requires continued assessment of disease activity, involving repeated sedation, endoscopy, and biopsy analysis. We investigated whether mucosal impedance measurements can be used to monitor disease activity in pediatric patients with EoE. Methods: We measured mucosal impedance at 3 locations in the esophagus in pediatric patients (1–18 years old; 32 with active EoE, 10 with inactive EoE, 32 with non-erosive reflux disease [NERD]) and 53 children with symptoms but normal findings from histologic analyses (controls) undergoing routine esophagogastroduodenoscopy at the Vanderbilt Pediatric Gastroenterology Clinic. Pathologists reviewed biopsies per routine protocol, determined eosinophilic density, and graded spongiosis on an ordinal visual scale. Mucosal impedance measurements were compared within patient groups. The primary outcome was correlation of mucosal impedance measurements with disease activity, based on severity of spongiosis and eosinophil counts. Results: Mucosal impedance measurements were significantly lower in patients with active EoE at 2, 5, and 10 cm above the squamo-columnar junction (median values of 1069, 1368, and 1707, respectively) compared to patients with inactive EoE (median values of 3663, 3657, and 4494, respectively), NERD (median values of 2754, 3243, and 4387), and controls (median values of 3091, 3760, and 4509) (P 

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Global Variation in Use of Enteral Nutrition for Pediatric Crohn Disease

Objectives: Exclusive enteral nutrition (EEN) is an effective induction treatment for pediatric Crohn disease. Given the center-based variation in use and diversity in practice we constructed a survey aimed at sharing experience and strategies in administering EEN, stimulating further research, and optimizing therapy. Methods: This survey was constructed after consultation with experts and designed to address key knowledge gaps. The survey was disseminated through the Paediatric IBD Porto Group of ESPGHAN, Canadian Children IBD Network, selective experts, and was sent twice through the PEDGI-BB. Data were collected into REDCap and analyzed using descriptive statistics. Results: In total, 146 participants from 26 countries completed the survey. Sixty-five percent of participants were general, non-IBD-focused pediatric gastroenterologists, 21% were IBD-focused, and 10% were dietitians. The most common indications (∼90% use) were for ileocecal and ileocolonic disease (Paris L1 and L3). The most common duration was 8 weeks and 66% preferred oral to nasogastric administration. Most (63%) did not allow any additional intake and 69% instructed patients to continue partial EN after completing treatment. Dietitians were identified as essential to EEN success while the primary challenges of EEN programs were adherence and lack of support. Regional and professional practice differences were observed in EEN indication, age, exclusivity, program structure/support, and cost coverage. Conclusions: We found significant variation in practice and use of EEN with several regional and professional differences. Global variation offers opportunities for research and improving care. This survey establishes a framework and provides resources for collaboration and information sharing. Address correspondence and reprint requests to Eytan Wine, MD, PhD, FRCPC, Division of Pediatric Gastroenterology and Nutrition, Department of Pediatrics, University of Alberta, Edmonton Clinic Health Academy, Room 4-577, 11405 87th Avenue, Edmonton AB, T6G 1C9, Canada (e-mail: wine@ualberta.ca). Received 15 December, 2017 Accepted 4 February, 2018 Funding source: N/A. The Authors declare no relevant conflicts of interest. Author contribution: ML performed data analysis, drafted the results, and wrote the first draft of the manuscript. JWW assisted with study design, helped draft the manuscript, and performed data analysis. VMNL coordinated data collection from Spain, preformed data analysis, and helped draft the manuscript. HQH assisted with study design and helped draft the manuscript. MWC assisted with study design and helped draft the manuscript. MC assisted with study design and helped draft the manuscript. PM assisted with study design, constructed the survey database, and helped draft the manuscript. ASD provided key data for the study and helped draft the manuscript. SH provided key data for the study and helped draft the manuscript. RSB assisted with the study concept and design and helped draft the manuscript. AL assisted with the study concept and design and helped draft the manuscript. EW initiated the study, constructed the survey, invited participants, supervised the project, performed data analysis, and wrote the manuscript. All the authors approved the final version of the paper. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Nutritional Status the First Two Years of Life in Cystic Fibrosis Diagnosed by Newborn Screening

Objective: To evaluate nutritional status and associated factors in a cystic fibrosis (CF) cohort diagnosed by newborn screening and followed up to month 24. Methods: A prospective longitudinal multicenter study assessing nutritional status according to pancreatic status, feeding modalities, prescriptions, pulmonary outcome and biological nutritional parameters. Results: One-hundred-and-five infants were recruited and 99 completed the study. Nutritional care management prevented undernutrition and stunting in those with exocrine pancreatic sufficiency (EPS), but affected (13/87) 15% and (21/86) 24%, respectively, of infants with exocrine pancreatic insufficiency (EPI). The logistic regression model found a positive association between both weight and length z-scores "at risk" at month 24, and initial pulmonary symptoms (OR 0.06, p 

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Dose-response Relationship Between Donor Human Milk, Mother's Own Milk, Preterm Formula, and Neonatal Growth Outcomes

Background: A dose-response relationship between proportions of donor human milk (DHM) intake and in-neonatal intensive care unit (in-NICU) growth rates, if any, remains poorly defined. Objective was to evaluate interrelationships between percentages of DHM, mother's own milk (MOM), and preterm formula (PF) intake and neonatal growth parameters at 36 weeks postmenstrual age or NICU discharge. Methods: Infants eligible for this single-center retrospective study were inborn at ≤32 weeks gestation or ≤1800 g, stayed in the NICU for ≥7 days, and received enteral nutrition consisting of human milk fortified with Enfamil human milk fortifier acidified liquid. Study exposures were defined as 10% increments in the total volumetric proportions of infant diet provided as MOM, DHM, or PF. Outcomes were growth parameters at 36 weeks postmenstrual age or NICU discharge. Multivariable linear regression modeled the adjusted additive effect of infant diet on individual growth parameters. Results: A total of 314 infants records were eligible for analysis. Using MOM as reference, the adjusted mean growth velocity for weight significantly decreased by 0.17 g · kg−1 · day−1 for every 10% increase in DHM intake, but did not vary with PF intake. The adjusted mean change in weight z score significantly decreased with increasing proportion of DHM intake but significantly improved with increasing PF intake. The adjusted mean head circumference velocity was significantly decreased by 0.01 cm/wk for every 10% increase in DHM intake, in reference to MOM, but did not vary with PF intake. Neither proportion of DHM nor PF intake was associated with length velocity. Conclusions: When DHM and MOM are fortified interchangeably, preterm infants receiving incremental amounts of DHM are at increased risk of postnatal growth restriction. The dose-response relationship between DHM, MOM, and PF and long-term growth and neurodevelopmental outcomes warrants further research. Address correspondence and reprint requests to Elizabeth A. Brownell, PhD, MA, Division of Neonatology, Connecticut Human Milk Research Center, Connecticut Children's Medical Center, Connecticut Children's Medical Center, 282 Washington St, Hartford, CT 06106 (e-mail: EBrownell@ConnecticutChildrens.org). Received 10 November, 2017 Accepted 15 February, 2018 The authors report no conflicts of interest. © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Ileal Obstruction secondary to Strangulation of the Ventriculoperitoneal Shunt Catheter

No abstract available

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Systematic Review: the Epidemiology, Natural History and Burden of Alagille Syndrome

Background: Alagille syndrome (ALGS) is an inherited multisystem disorder typically manifesting as cholestasis, and potentially leading to end-stage liver disease and death. Aim: To perform the first systematic review of the epidemiology, natural history and burden of ALGS with a focus on the liver component. Methods: Electronic databases and proceedings from key congresses were searched in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines. This analysis included publications reporting epidemiology, natural history, economic burden or health-related quality of life (HRQoL) outcomes in patients with ALGS. Results: Of 525 screened publications, 20 met the inclusion criteria. Liver-related features included cholestasis (87–100% of patients), jaundice (66–85%) and cirrhosis (44–95%). Between 15% and 47% of patients underwent liver transplantation and 4–14% received partial biliary diversion. Pruritus affected the majority of patients (59–88%, of whom up to 45% had severe pruritus) and manifested during the first 10 years of life. Children with ALGS had significantly impaired HRQoL compared with healthy controls and those with other diseases. Itching was the symptom that most affected children with ALGS. No study assessed the economic burden of ALGS. Conclusions: Our findings consolidate information on the clinical course of ALGS, and highlight gaps in knowledge, most notably the absence of any research on the economic consequences of the disease. Further research is needed to establish the incidence of genetically confirmed ALGS. Disease-specific tools are also needed to improve the measurement of symptoms, such as itching, and better understand the impact of ALGS on HRQoL. Address correspondence and reprint requests to Dr B.M. Kamath, MBBChir, MRCP, MTR, Division of Gastroenterology, Hepatology and Nutrition, Hospital for Sick Children, University of Toronto, Toronto, Canada (e-mail: binita.kamath@sickkids.ca). Received 10 March, 2017 Accepted 24 February, 2018 Address for reprints: Same as above. Conflicts of interest and sources of funding: Declaration of funding interests: Research was funded by Shire International GmBH. Under the direction of the authors, Dr Kim Wager, an employee of Oxford PharmaGenesis, provided writing assistance for this publication. Editorial assistance in formatting, proofreading, copy editing, and fact checking was also provided by Oxford PharmaGenesis. Shire International GmBH provided funding to Oxford PharmaGenesis for support in writing and editing this manuscript. Declaration of personal interests: Dr Kamath has served as a speaker and consultant for Retrophin and has received travel expenses from Shire Pharmaceuticals. Dr Baker has received research funding from Shire Pharmaceuticals. Prof Dr Houwen has served as a consultant for Albireo. Lora Todorova is an employee of Shire Pharmaceuticals. Prof Kerkar has served as an advisory board member for Retrophin and Alexion. Trial information: Not applicable. Sources of funding: Not applicable. Specific author contributions: All authors had equal responsibility for the design, conduct and approval of the final version of the manuscript. Supplemental digital content is available for this article. Direct URL citations appear in the printed text, and links to the digital files are provided in the HTML text of this article on the journal's Web site (www.jpgn.org). © 2018 by European Society for Pediatric Gastroenterology, Hepatology, and Nutrition and North American Society for Pediatric Gastroenterology,

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Development and evaluation of a passive trunk support system for Duchenne muscular dystrophy patients

Patients with Duchenne muscular dystrophy gradually lose the ability to use different muscles of their body. Consequently, they lose the ability to stabilize their trunk against gravity. This hinders them to e...

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Splice-site mutations in VEGFC cause loss of function and Nonne-Milroy-like primary lymphedema

Thumbnail image of graphical abstract

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A case of duodenal malignant lymphoma presenting as acute pancreatitis: systemic lupus erythematosus and immunosuppressive therapy as risk factors

Abstract

A 49-year-old man was admitted to our hospital with pancreatitis. He was diagnosed with systemic lupus erythematosus at 34 years of age and was being treated with oral tacrolimus (3 mg/day) and predonine (10 mg/day) for the past 15 months. The computed tomography (CT) scan showed the mass lesion had invaded the pancreatic head via thickening of the duodenal wall. Upper gastrointestinal endoscopy showed the all-round ulcerative lesion from the superior duodenal angle to the descending portion. Histological examination confirmed the diagnosis of diffuse large B cell lymphoma (DLBCL). Tacrolimus therapy was stopped due to the possibility of immunodeficiency-related lymphoproliferative disease; however, the lesion did not improve. Consequently, he was administered rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). After six courses of R-CHOP therapy, a partial response was confirmed on CT. One month after the completion of chemotherapy, a gastrojejunal anastomosis was performed because of duodenal stenosis. He has since been well without recurrence. It was difficult to identify the risk factor for DLBCL; therefore, both the disease activity and immunosuppressive therapy should be taken into consideration as carrying a risk. In the present case, the symptom of pancreatitis enabled an early diagnosis of DLBCL.



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The Effects of an Oral Taurine Dose and Supplementation Period on Endurance Exercise Performance in Humans: A Meta-Analysis

Abstract

Background

Taurine is central to many physiological processes, some of which are augmented by exogenous supply and have the potential to facilitate endurance performance; however, its independent effects on performance have not been systematically analysed.

Objective

To evaluate the effects of isolated oral taurine ingestion on endurance performance and to assess the contribution of (1) the dose and (2) the supplementation period to the ergogenic effect.

Methods

A search was performed using various databases in September 2017. The studies were screened using search criteria for eligibility. Ten peer-reviewed articles were identified for inclusion. A sub-analysis of time-to-exhaustion (TTE) trials (n = 7) was also performed. The effects of (1) dose and (2) the acute (single dose) or chronic (> 1 day) supplementation periods were assessed using meta-regression. The doses of taurine ranged from 1 to 6 g/day and were provided in single doses and for up to 2 weeks among a range of subjects.

Results

Taurine ingestion improved overall endurance performance (Hedges' g = 0.40, 95% CI 0.12–0.67, P = 0.004), which was similar in TTE trials (Hedges' g = 0.43, 95% CI 0.12–0.75, P = 0.007). There were no differences between acute or chronic supplementation for the full sample (P = 0.897) or the TTE group (P = 0.896). The dose of taurine did not moderate its effect on endurance performance (P > 0.05).

Conclusion

Human endurance performance can be improved by orally ingesting a single dose of taurine in varying amounts (1–6 g).



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The Other and Me: Effects of oxytocin on self-other distinction

Publication date: Available online 14 March 2018
Source:International Journal of Psychophysiology
Author(s): L. Tomova, M. Heinrichs, C. Lamm
Distinguishing self- from other-related representations plays an important role in social interactions. The neuropeptide oxytocin has been shown to modulate social behavior as well as underlying social cognitions and emotions. However, how exactly oxytocin modulates representations of self and other is still unclear. The present study therefore aimed to assess effects of oxytocin on self-other distinction on two different processing levels (i.e., lower-level imitation-inhibition and higher-level perspective taking) in a male sample (n = 56) by performing a double-blind, placebo-controlled oxytocin administration study. Oxytocin improved visual perspective-taking and thus affected self-other distinction on the cognitive level, but had no effects on self-other distinction on the perceptual-motor level nor on a control task measuring attention reorientation. Thus, our findings suggest that oxytocin reduces ambiguity during perspective-taking in social interactions, which in turn may encourage social approach motivation and affiliative behavior.



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Airway management through submental derivation: a safe and easily reproduced alternative for patients with complex facial trauma.

Airway management through submental derivation: a safe and easily reproduced alternative for patients with complex facial trauma.

J Korean Assoc Oral Maxillofac Surg. 2018 Feb;44(1):12-17

Authors: González-Magaña F, Malagón-Hidalgo HO, García-Cano E, Vilchis-López R, Fentanes-Vera A, Ayala-Ugalde FA

Abstract
Objectives: Airway management in patients with panfacial trauma is complicated. In addition to involving facial lesions, such trauma compromises the airway, and the use of intermaxillary fixation makes it difficult to secure ventilation by usual approaches (nasotracheal or endotracheal intubation). Submental airway derivation is an alternative to tracheostomy and nasotracheal intubation, allowing a permeable airway with minimal complications in complex patients.
Materials and Methods: This is a descriptive, retrospective study based on a review of medical records of all patients with facial trauma from January 2003 to May 2015. In total, 31 patients with complex factures requiring submental airway derivation were included. No complications such as bleeding, infection, vascular, glandular, or nervous lesions were presented in any of the patients.
Results: The use of submental airway derivation is a simple, safe, and easy method to ensure airway management. Moreover, it allows an easier reconstruction.
Conclusion: Based on these results, we concluded that, if the relevant steps are followed, the use of submental intubation in the treatment of patients with complex facial trauma is a safe and effective option.

PMID: 29535964 [PubMed]



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Assessing breath-by-breath alveolar gas exchange: is the contiguity in time of breaths mandatory?

Abstract

Purpose

A new algorithm is illustrated for the determination of breath-by-breath alveolar gas exchange that neglects the contiguity in time of breaths, i.e. it allows the breaths to be partially superimposed or disjoined in time.

Methods

Traces of oxygen, carbon dioxide fractions, and ventilatory flow were recorded continuously over 20 min in 15 healthy subjects in resting conditions; at 5-min intervals, subjects voluntarily hyperventilated for ~ 30 s to induce abrupt changes in lung gas stores. Gas exchange data were calculated applying the new algorithm and were compared to those yielded by a reference algorithm, also providing values at the alveolar level.

Results

Average O2 uptakes (V′O2) obtained with the two algorithms were similar during quiet breathing (0.28 ± 0.06 vs. 0.29 ± 0.06 L/min; two-sided paired t test, n = 45, p = NS); during hyperventilation, average V′O2 was significantly lower applying the new algorithm compared to the reference algorithm (0.57 ± 0.15 vs. 0.65 ± 0.17 L/min; difference − 0.077 ± 0.048 L/min; two-sided paired t test, n = 45, p < 0.001). The first breath of each hyperventilation manoeuvre showed the greatest difference in V′O2 (− 0.25 ± 0.23 L/min, z test against zero, n = 45, p < 0.001). The volumes of O2 considered twice (or neglected) because of the lack of contiguity of breaths were overall small (maximum of 3 mL) and, if accounted for, had only a slight softening effect on the fluctuations of the O2 uptake.

Conclusion

The new algorithm, which assumes each breath as the leading subject, was able to effectively account for changes in lung gas stores without requiring any predetermined value or off-line optimisation procedure.



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Genetic alterations affecting the kynurenine pathway and their association with diseases

Publication date: Available online 14 March 2018
Source:Mutation Research/Reviews in Mutation Research
Author(s): Fanni Boros, Zsuzsanna Bohár, László Vécsei
Tryptophan is metabolized primarily via the kynurenine pathway (KP). The KP involves several enzymes, including indoleamine 2,3-dioxygenase, tryptophan 2,3 dioxygenase (TDO2), kynurenine aminotransferases (KATs), kynurenine monooxigenase (KMO) etc. The majority of metabolites are neuroactive, some of them such as kynurenic acid show neuroprotective effects, while others, for example 3-hydroxy-L-kynurenine and quinolinic acid contribute to free radical production, leading to neurodegeneration. Impaired balance of the pathway is assumed to participate in the development of several diseases such as Parkinson's disease, Huntington's disease, Alzheimer's disease, psychiatric disorders, migraine and multiple sclerosis.The aim of this review is to summarize available literature data on genetic alterations of the KP, leading to disturbances of the pathway that can be related to different diseases.To achieve this goal, literature search was executed regarding the genetic alterations of enzymes related to the KP until April 2017 based on PubMed.Several genetic alterations of the KP were found, and suggested to be associated with diseases. Polymorphisms of the TDO2 gene can be associated with autism; KATII polymorphisms affect the immune response of patients with bacterial meningitis, mutations of the KMO gene can be associated with multiple sclerosis and cognitive functions in schizophrenia, just to mention a few.To our knowledge, this is the first comprehensive review of the genetic alterations of the KP enzymes. This work can promote the understanding of the mechanisms underlying the connected diseases, and might facilitate medicinal chemistry approaches to substitute missing components or correct the disturbed metabolite balance of KP.



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Neuraxial labor analgesia: a focused narrative review of the 2017 literature

Purpose of review Neuraxial labor analgesia remains the most effective and one of the most commonly utilized methods for pain relief during labor. This narrative review article is a summary of the literature published in 2017 on neuraxial analgesia for labor. Recent findings From a total of 41 identified articles, 13 were included in the review. The topics have been structured into three categories: initiation of neuraxial analgesia, maintenance of neuraxial analgesia, and neuraxial analgesia and obstetric outcomes. Maintenance regimens, such as program intermittent epidural bolus (PIEB) techniques, remain a focus of extensive research with the potential to optimize analgesia for each individual patient. In a similar way, the dural puncture epidural technique could improve the quality of labor analgesia with fewer side effects compared with standard epidural and combined spinal epidural (CSE) techniques. Finally, the increased use of modern technology using portable ultrasound devices with automated imaging software to facilitate epidural catheter placement may offer potential advantages to the obstetric anesthesiologist, especially when dealing with technically difficult cases. Summary Recent advances, as well as refinements, of current neuraxial analgesia techniques could improve women's experience of labor. Correspondence to Mitko Kocarev, Anesthesia Department, Hamad Medical Corporation, PO Box 3050, Doha, Qatar. E-mail: mkocarev@hamad.qa Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Paediatric anaesthesia: a rapidly evolving subspecialty

No abstract available

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Wellness in anaesthesia

No abstract available

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Peer support in anesthesia: turning war stories into wellness

Purpose of review Peer support, a method of providing for the well being of healthcare providers following adverse or stressful events, is garnering increased attention in light of the increased prevalence and awareness of burnout, depression and suicidality in physicians. In this review, we will summarize the evolution of the 'second victim,' explore methods of support and examine how new regulatory requirements are changing the peer support landscape. Recent findings As peer support and the second victim are investigated more, themes are emerging regarding the natural history of recovery. As these are delineated, more targeted peer support models are being developed. One major change in 2017 is the institution of new Accreditation Council for Graduate Medical Education's Common Program Requirements, now including topics targeted on well being. Summary Effective and accessible peer support is developing in many departments nationwide and can only be expected to continue, given new regulatory requirements. As these programs develop, and research on their effect continues, best practices will likely emerge. Correspondence to Amy E. Vinson, MD, Boston Children's Hospital, 300 Longwood Avenue - Bader 3, Boston, MA 02115, USA. Tel: +1 401 261 4642; e-mail: amy.vinson@childrens.harvard.edu Copyright © 2018 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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